A method of treating a proliferative disease, disorder, or condition comprising:nadministering to a subject in need thereof a therapeutically effective amount ofn(a) an MDM2 inhibitor; and(b) an EGFR inhibitor;wherein the MDM2 inhibitor comprises a compound having a formula of:
›2.↳ 1The method of claim 1, wherein the proliferative disease, disorder, or condition comprises cancer.d2
The method of claim 1, wherein the proliferative disease, disorder, or condition comprises cancer.
›3.↳ 1The method of claim 1, wherein administering the MDM2 inhibitor and the EGFR inhibitor results in a synergistic reduction in cell proliferation in a t…d2
The method of claim 1, wherein administering the MDM2 inhibitor and the EGFR inhibitor results in a synergistic reduction in cell proliferation in a tumor of the subject or a synergistic increase in apoptosis in a tumor of the subject as compared to administration of either the MDM2 inhibitor or the EGFR inhibitor alone.
›4.↳ 1The method of claim 1, comprising administering to a subject in need thereof a therapeutically effective amount of (i) a pharmaceutical composition co…d2
The method of claim 1, comprising administering to a subject in need thereof a therapeutically effective amount of (i) a pharmaceutical composition comprising an MDM2 inhibitor, an EGFR inhibitor, and a pharmaceutically acceptable carrier or excipient or (ii) a first pharmaceutical composition comprising an MDM2 inhibitor and a pharmaceutically acceptable carrier or excipient and a second pharmaceutical composition comprising an EGFR inhibitor and a pharmaceutically acceptable carrier or excipient.
›5.↳ 1The method of claim 1, wherein the subject has one or more of: (i) an inactivating P53 mutation or deletion in the subject; (ii) a defect in an upstre…d2
The method of claim 1, wherein the subject has one or more of: (i) an inactivating P53 mutation or deletion in the subject; (ii) a defect in an upstream component of a p53 pathway; (iii) a defect in a downstream component of the p53 pathway; (iv) increased expression an MDM2 gene as compared to a control; (v) increased levels of MDM2 protein as compared to a control; or (vi) resistance to treatment with an EGFR inhibitor alone.
›6.↳ 1The method of claim 1, comprising selecting or modifying a treatment on the basis of detecting in a subject one or more of (i) an inactivating P53 mut…d2
The method of claim 1, comprising selecting or modifying a treatment on the basis of detecting in a subject one or more of (i) an inactivating P53 mutation or deletion in the subject; (ii) a defect in an upstream component of a p53 pathway; (iii) a defect in a downstream component of the p53 pathway; (iv) increased expression an MDM2 gene as compared to a control; (v) increased levels of MDM2 protein as compared to a control; or (vi) resistance to treatment with an EGFR inhibitor alone.
›7.↳ 1The method of claim 1, wherein the EGFR inhibitor is selected from the group consisting of cetuximab, panitumumab, nimotuzumab, zalutumumab, matuzumab…d2
The method of claim 1, wherein the EGFR inhibitor is selected from the group consisting of cetuximab, panitumumab, nimotuzumab, zalutumumab, matuzumab, potato carboxypeptidase inhibitor, gefitinib, lapatinib, and erlotinib, or a combination thereof.
›8.↳ 1The method of claim 1, wherein the EGFR inhibitor is erlotinib.d2
The method of claim 1, wherein the EGFR inhibitor is erlotinib.
›9.↳ 1The method of claim 1, wherein the MDM2 inhibitor (i) inhibits MDM2 activity; (ii) increases phosphorylated p53; (iii) re-activates p53; (iv) inhibits…d2
The method of claim 1, wherein the MDM2 inhibitor (i) inhibits MDM2 activity; (ii) increases phosphorylated p53; (iii) re-activates p53; (iv) inhibits binding of p53 and MDM2; or a combination thereof.
›10.↳ 1The method of claim 1, wherein the MDM2 inhibitor comprises a compound having a formula of:d2+1
The method of claim 1, wherein the MDM2 inhibitor comprises a compound having a formula of:
›14.↳ 10The method of claim 10, whereinnthe EGFR inhibitor is erlotinib; andthe proliferative disease, disorder, or condition comprises cancer.d3
The method of claim 10, whereinnthe EGFR inhibitor is erlotinib; andthe proliferative disease, disorder, or condition comprises cancer.
›11.↳ 1The method of claim 1, wherein the MDM2 inhibitor comprises a compound selected from the group consisting of:d2
The method of claim 1, wherein the MDM2 inhibitor comprises a compound selected from the group consisting of:
›12.↳ 1The method of claim 1 wherein the proliferative disease, disorder, or condition comprises one or more of the group consisting of cancer; blood vessel …d2
The method of claim 1 wherein the proliferative disease, disorder, or condition comprises one or more of the group consisting of cancer; blood vessel proliferative disorders; fibrotic disorders; mesangial cell proliferative disorders; psoriasis; actinic keratoses; seborrheic keratoses; warts; keloid scars; eczema; hyperproliferative diseases caused by virus infections; and papilloma virus infection.
›13.↳ 1The method of claim 1, whereinnthe EGFR inhibitor is erlotinib; andthe proliferative disease, disorder, or condition comprises cancer.d2
The method of claim 1, whereinnthe EGFR inhibitor is erlotinib; andthe proliferative disease, disorder, or condition comprises cancer.
